Surface resistance to protein adsorption is important for many applications, such as coatings for ship hulls, implanted biomaterials, biomedical diagnostics and sensors, bioseparations, and drug delivery. For example, marine biofouling leads to problems ranging from propulsive fuel losses due to increased drag to reduced capacity for speed and range. Many hydrophilic surfaces can reduce protein adsorption. However, these surfaces are often not sufficient to prevent the undesirable adhesion of cells, bacteria, or other microorganisms. Even a small amount of proteins on a surface can lead to the adhesion and propagation of unwanted fouling. For example, fibrinogen adsorption less than 5-10 ng/cm2 is needed to inhibit platelet adhesion for blood compatibility and superlow fouling surfaces are required for these applications. Nonfouling materials have the ability to prevent nonspecific protein adsorption from the surfaces coated with these materials. Surface or material resistance to protein adsorption and cell/microorganism adhesion is critical to the development of environmentally friendly antifouling or nonfouling paints for marine application, biomaterials with superior compatibility, and biosensors with high specificity.
Traditionally, the best antifouling coating for marine application is TBT (tributyltin)-based paint. Due to increased environmental concern over the effects of TBT on non-target marine organisms, particularly in areas of low water exchange such as coastal estuaries and marinas, TBT antifouling coatings have been restricted in many countries including the United States. The TBT-free antifouling paint in the current market is based on non-tin biocide, such as copper particles or cuprous oxide. Because these paints leach copper into water, these biocides are harmful to the marine environment, and their application is highly limited. Non-toxic, fouling-release silicone and fluorinated coatings are under development. However, these coatings are only effective on vessels moving at high speeds. As fouling occurs most readily on static structures or ship moving slowly in seawater close to land, the application of these coatings is highly limited. There is a need for environmentally friendly nonfouling coatings to which marine microorganisms do not attach.
A variety of polymers have been used as biocompatible materials in biomedical fields. However, only a few candidates are regarded as “non-fouling materials” or “superlow fouling materials”. Poly(ethylene glycol) (PEG)-based materials are the most commonly used nonfouling materials. PEG or oligo(ethylene glycol) (OEG) modified surfaces have been extensively studied to resist nonspecific protein adsorption. Steric exclusion effect was considered as one of the reasons for PEG polymers to resist protein adsorption. Studies of OEG self-assembled monolayers (SAMs) show that the appropriate surface density of OEG chains is needed for surface resistance to protein adsorption and a tightly bound water layer around OEG chains is mainly responsible for large repulsive hydration forces. However, PEG or OEG group auto-oxidizes relatively rapidly, especially in the presence of oxygen and transition metal ions and most biochemically relevant solutions contain transition metal ions. It has also been shown that grafted PEG brushes exhibit protein resistance at room temperature, but lose their protein repulsive properties above 35° C. It is of great interest to search for alternative nonfouling materials other than PEG.
Phosphorylcholine (PC)-based polymers or surfaces have been shown to decrease protein adsorption. They are considered as biomimetic fouling-resistant materials because they contain phosphorylcholine headgroups, which are found in the outside layer of cell membranes. The majority of work relating to phosphorylcholine (PC)-based materials is on methacryloyloxyethyl phosphorylcholine (MPC)-based copolymers with the PC group located in the side chains, such as MPC-co-BMA (butylmethacrylate). MPC-based copolymers have been used commercially in contact lenses. An alternative approach is to form PC-terminated self-assembly monolayers (SAMs) on gold. Fibrinogen adsorption as low as 18% of a ML (monolayer) with respect to that on methyl-terminated SAMs has been reported. The hydration of PC-based materials is also thought to be the reason for their resistance to protein adsorption. However, the phosphoester group is susceptible to hydrolysis, and PC monomers, such as 2-methacryloyloxyethyl phosphorylcholine (MPC), are moisture sensitive and not easy to synthesize and handle. It is desirable to develop new materials other than PC for applications requiring long-term material stability.
Similar to phosphorylcholine-based polymers, sulfobetaine polymers belong to polybetaine polymers, in which both cationic and anionic groups are on the same monomer residue. Compared to MPC, sulfobetaine methacrylate (SBMA) is easier to synthesize and handle. However, SBMA polymers were thought to be less fouling-resistant than PC polymers. Because most previous studies of SBMA polymers concentrated on their copolymers with other hydrophobic monomers in order to attach them onto substrates or provide mechanical strength, the potential of sulfobetaines as non-fouling materials or biocompatible materials has been underestimated.
Segmented polyurethane (SPU) is one of the widely used biomaterials, especially in cardiovascular devices, due to its excellent mechanical properties. A series of studies have reported on improving its biocompatibility with MPC-based polymers via surface grafting, polymer blending, or interpenetrating polymer networks (IPNs). Ishihara and co-workers have performed extensive studies of MPC/SPU films that form a stable cross-linked network and effectively reduce platelet adhesion as compared to the original SPU. Morimoto, K. et al. Biomaterials 23:4881-87, 2002; Morimoto, K. et al. Biomaterials 25:5353-61, 2004. Because of the moisture sensitivity of MPC monomer, it is desirable to develop new SPU-based materials other MPC/SPU films with super-low fouling characters.
A need therefore exists for super-low fouling materials. In this way, the super-low fouling material can be used in making super-low fouling surfaces that are useful in coatings for ship hulls, implanted biomaterials, biomedical diagnostics sensors, drug delivery. These and other objectives are accomplished by the invention set forth below.